1. Field of the Invention
This invention relates generally to the fields of molecular biology and molecular medicine and more specifically to the identification of proteins involved in programmed cell death and associations of these proteins.
2. Background Information
Programmed cell death is a physiologic process that ensures homeostasis is maintained between cell production and cell turnover in essentially all self-renewing tissues. In many cases, characteristic morphological changes, termed "apoptosis," occur in a dying cell. Since similar changes occur in different types of dying cells, cell death appears to proceed through a common pathway in different cell types.
In addition to maintaining tissue homeostasis, apoptosis also occurs in response to a variety of external stimuli, including growth factor deprivation, alterations in calcium levels, free-radicals, cytotoxic lymphokines, infection by some viruses, radiation and most chemotherapeutic agents. Thus, apoptosis is an inducible event that likely is subject to similar mechanisms of regulation as occur, for example, in a metabolic pathway. In this regard, dysregulation of apoptosis also can occur and is observed, for example, in some types of cancer cells, which survive for a longer time than corresponding normal cells, and in neurodegenerative diseases where neurons die prematurely. In viral infections, induction of apoptosis can figure prominently in the pathophysiology of the disease process.
Some of the proteins involved in programmed cell death have been identified and associations among some of these proteins have been described. However, the mechanisms by which these proteins mediate their activity remains unknown. The identification of the proteins involved in cell death and an understanding of the associations between these proteins can provide a means for manipulating the process of apoptosis in a cell and, therefore, selectively regulating the relative lifespan of a cell.
A cell surface protein known as Fas (also called APO-1 and CD95; hereinafter "Fas"), which is expressed on various types of human cells, including breast, colon, prostate and pancreatic cancer cells, can trigger apoptosis. Fas is a member of the tumor necrosis factor receptor (TNFR) family of proteins, which also includes, for example, the nerve growth factor receptor. These receptor proteins transduce extracellular signals into a cell and, as a result, can induce cell death or promote cell survival. However, the mechanism by which cell surface receptors such as Fas regulate cell death is not known.
Since Fas is present on the cell surface, its action likely is mediated by Fas binding to one or more intracellular proteins, which ultimately effect cell death. The identification of euch intracellular proteins that can associate with Fas and, therefore, can be involved in apoptosis would allow for the manipulation of this association as a means to modulate apoptosis in a cell. Thus, a need exists to identify proteins that associate with Fas. The present invention satisfies this need and provides additional advantages as well.